The personal blog of Dave Fernig, thoughts on science and unrelated matters

How neuropilin-1 binds heparin/heparan sulfate and publishing in the PeerJ

Kat’s paper on the interactions of neuropilin-1 with a heparan sulfate mimetic library of modified heparins is now published in The PeerJ
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The paper is very interesting, because the data intrigue and puzzle. Our interpretation of how FcNRP-1 binds the polysaccharide is that the sugar “snakes” along the protein surface – think of the classic shot of a sidewinder rattlesnake moving across the sand, where the snake is the polysaccharide and the sand the protein surface. So a far more dynamic view of a protein-glycosaminoglycan interaction than we had held previously. An intriguing observation is that neuropilin-1 binds completely desulfated heparin and does so far better than any other heparin-binding protein we have studied. A major puzzle is the observation that shNRP-1 binds heparin very weakly. Thoughts on these and other aspects most welcome – put them directly up at the PeerJ, since the journal provides a commenting facility.

The paper also reflects what I consider to be a problem in molecular life sciences. We are sheep and all head off in the same direction. Neuropilin is a fascinating protein. It has a large number of protein partners (West et al., 2005) and is involved in many diverse biological functions. It can act as a co-receptor for VEGF and as a pure VEGFR agonist (Uniewicz et al., 2011). Despite this it is a minority sport, with just a handful of labs working on it, whereas other proteins of no greater functional importance have hundreds of labs dedicated to understanding the intricacies of their functions. A bit more diversity would at the very least be a great help in annotating genomes…

And now, time for a confession. I have a really, really bad hangover. Sadly, not from overindulging at the table, but a hangover of manuscripts. These are not bits lying around, but good drafts that need discussion and due care and attention. The cause of the hangover? My excuse is being over stretched, which may stem from my generally enthusiastic response to demands on my time. Being head of department or its equivalent for six years hasn’t helped and I am still recovering from my role as REF coordinator (the timescale of recovery from REF seems almost geological).
For the first time, this year I actually made two resolutions, one of which was to submit a paper a month to clear the dangerous (from a health and safety perspective!) overhang of manuscripts in my office. Kat’s paper is the third (March) paper.

Why PeerJ? At a personal level, I have got tired/bored/ennui/cafard of that aspect of reviewing, which does not look at the data, but instead applies some sort of “novelty” threshold. I started my PhD 33 years ago and one thing is obvious: those “novel” papers in bright shiny journals did not stand the test of time any better than those published in so-called lesser journals. Conversely, I go back repeatedly to papers, probably deemed “thorough, but boring” at the time. Reviewing manuscripts is often very annoying. I provide critiques of the data, the other reviewers have clearly not bothered to look at these and have evaluated only the “novelty” factor. I took hours, they took 15 min. I also get very frustrated reading a paper where there are bright shiny pictures depicting quantitative data, but those data are conspicuously absent. I like to fit data together, yours and ours, because this helps me build a “worldview”.

The lab is low on funds (this has almost always been true, we are very productive, so have almost enough funds) and, since the authors were not funded by RCUK or the Wellcome Trust, there were no funds for OA publishing. The PeerJ model looked interesting, so I took the plunge. This was a very satisfying experience and one that also taught me a few things. In hindsight these are completely obvious and reflect more on how slow we adapt to new circumstances (and data…). The main lesson relates to supplementary information. I can remember miniprints in J Biol. Chem., a means to include details on methods and save paper. The electronic journal converted this idea into supplementary information. This is where we would put lots of data, keeping the paper short. All very well when you print, but in an electronic journal, this makes no sense. Supplementary information is for a defined subplot. If the reader isn’t too interested in examining a specific set of data, they just don’t click on the link. I figured this out too late for the neuropilin paper, but our next ones will have far less supplementary (the next one is now a preprint at The PeerJ and undergoing review).

Not all my biology papers will go to The PeerJ, because there are tensions. First, graduate students and postdocs are very aware of the problems of evaluation in science and that, though impact factors are thoroughly discredited, they are used extensively. So I have to make sure their wishes are respected. Second, I have to consider the Learned Societies. The profit from their journals is re-invested in science: running meetings, providing grants for young to attend meetings, grants for school teachers to do research and so on. Third, I collaborate a lot and would not want to impose on my collaborators, many of whom work in countries where impact factor is the difference between a career and no career.

As the landscape of science publishing and evaluation changes, I will for now stick to my second resolution: only publish in open access and learned society journals and only accept reviewing requests from these.

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[…] Gemma’s work on SmartFlares, which can be accessed via her supervisor’s blog, does have some parallels with the world of antisense two decades ago. The SmartFlares are polyanions. Protein recognition of extracellular polyanions (in vivo, glycosaminoglycans such as heparan sulfate) is dependent on charge, but is also selective, so the disposition of charges in space determines whether proteins will bind or not (posts on some papers I have been involved in here, here, and here). […]